| Role of the cholesterol biosynthetic pathway in osteoblastic differentiation. | |
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MedLine Citation:
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PMID: 17721067 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cholesterol (C27H46O) is the principal structural lipid of the biological membrane, but it also plays an important role in many other biological functions. Even though the majority of body cholesterol is synthesized by the liver and secreted as circulating lipoproteins, many cell types can synthesize cholesterol ex novo. The biosynthetic pathway of cholesterol proceeds through several intermediates and involves different enzymes. The rate-limiting step of cholesterol synthesis is the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that synthesizes mevalonate starting from HMG-CoA. Since natural inhibitors of HMG-CoA reductase, named statin, have been isolated, many others have been developed, which differ in their lipophilicity/ hydrophilicity. By using statins, many studies have been performed in order to shed light on the role of cholesterol on different cell types and, among these, on bone cells. In vivo studies have demonstrated that treatment of pluripotent mouse marrow stromal cells (M2-10B4) with statins inhibited the differentiation of these cells into osteoblastic cells, confirming the crucial role of cholesterol biosynthetic pathway for osteoblast differentiation. Conversely, other studies, using other cellular systems, have reported that statins may exert an anabolic effect on bone. Moreover, human and animal studies have shown that hypercholesterolemia may play an adverse effect in osteoporotic bone loss. In conclusion, it appears that cholesterol is important for different cellular activities, such as osteoblastic differentiation, if present in "normal" physiological concentration and particular experimental conditions, but it may exert adverse effects if present in excess. |
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Authors:
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G Viccica; E Vignali; C Marcocci |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Journal of endocrinological investigation Volume: 30 ISSN: 1720-8386 ISO Abbreviation: J. Endocrinol. Invest. Publication Date: 2007 |
Date Detail:
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Created Date: 2007-08-27 Completed Date: 2008-01-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7806594 Medline TA: J Endocrinol Invest Country: Italy |
Other Details:
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Languages: eng Pagination: 8-12 Citation Subset: IM |
Affiliation:
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Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acyl Coenzyme A
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metabolism Animals Cell Differentiation / physiology* Cholesterol / biosynthesis* Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry, metabolism Molecular Structure Osteoblasts / cytology, physiology* Osteogenesis / physiology |
| Chemical | |
Reg. No./Substance:
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0/Acyl Coenzyme A; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 1553-55-5/3-hydroxy-3-methylglutaryl-coenzyme A; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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